The principal focus of this project is the influence of sugar source upon the phenotype of mammalian cells in culture. Naturally occurring sugars other than glucose as well as sugar analogues have been used to achieve changes in cell growth, cell surface properties, sugar transport, and resistance to diphtheria toxin. The probable biochemical basis for the phenotypic modifications observed is glycosylation patterns resulting from altered nucleotide sugar pools. Since the nucleotide sugars are the precursors of glycopolymers, the composition of glycolipids, glycoproteins, and polysaccharides of the cell will depend to some degree upon the nucleotide sugar pools. Nucleoside analogues have been shown by us also to cause alterations in the cell parameters cited above. Nucleotide sugar pools can be shown to vary significantly upon addition of nucleoside analogues to the culture medium. Since some important anti-tumor agents are nucleoside analogues, we have turned to tumor cells and mice bearing experimental tumors to pursue the influence of sugars on those interactions. The sugars can be demonstrated to interfere with anti-tumor action by certain nucleoside analogues. A major effort links the regulation of glucose transport to nucleotide sugars as a cofactor in the turnover of transport carrier.